Recent evidence suggests that neurotransmitter precursor (choline) availability may be an important factor regulating the metabolism of acetylcholine in brain. Although data supporting a positive correlation between choline adinistration and the steady-state concentration of acetylcholine are conflicting, clinical studies indicate possible therapeutic merits of choline in the treatment of psychiatric and neurological disorders postulated to involve impaired cholinergic tone. Therefore, the basic objective of this research proposal is to elucidate the effects of exogenous choline, as modified by parenteral or dietary manipulation, on biochemical, pharmacological and behavioral parameters of central cholinergic activity. Animals will be maintained on choline deficient, standard choline or choline supplemented diets and acetlcholine turnover, steady-state neurotransmitter concentrations, high affinity choline uptake, cholinergic receptor characteristics and choline acetyltransferase and acetylcholinesterase activities will be analyzed in specific brain regions. In addition, the effects of choline on the functional activity of cholinergic neurons will be assessed by measurements of temperature regulation, appetitive behavior, spontaneous locomotor activity and neurological syndromes including circling behavior, catalepsy, tremor and stereotypy. The neuropharmacological implications of altered choline availability will be evaluated by measurements of the efficacy of pharmacological agents affecting central cholinergic neurons. Furthermore, the effects of choline on the biochemical and functional balance between acetylcholine and dopamine in the striatum will be investigated. These studies will undoubtedly provide information on the relationship between nutritional choline intake and the functional dynamics of acetylcholine and will provide a rational basis to assess the therapeutic merits of choline in the treatment of various psychiatric and neurological disorders.